PW549736 | Quorum Sensing: PlcR Biosynthesis | Reaction compounds not found | | The production of PlcR (pleiotropic regulator) in Bacillus thuringiensis and Bacillus cereus is a tightly regulated process that integrates quorum sensing, transcriptional regulation, and virulence factor production, ultimately contributing to biofilm formation. PlcR is a key transcriptional regulator that controls the expression of numerous virulence genes, including plcA, hbl, and inhA2, which play aid in biofilm development. The production of PlcR begins with the transcription of the plcR gene, which is autoregulated, meaning that PlcR binds to its own promoter to enhance its expression. This autoregulation ensures a positive feedback loop, amplifying PlcR production as the bacterial population grows. PlcR activity is further modulated by the PapR peptide, a quorum-sensing molecule. PapR is synthesized as a precursor peptide (pre-PapR) in the cytoplasm, processed by signal peptidases, and secreted into the extracellular space via the Sec secretion system. Once extracellular PapR reaches a threshold concentration, it is re-imported into the cell via the oligopeptide permease (Opp) system, where it binds to and activates PlcR. The active PlcR-PapR complex then binds to specific DNA sequences (PlcR boxes) in the promoter regions of target genes, including plcA, hbl, and inhA2, activating their transcription.The products of these PlcR-regulated genes play critical roles in biofilm formation. For example, PlcA (phosphatidylinositol-specific phospholipase C) hydrolyzes phosphatidylinositol in host cell membranes, releasing diacylglycerol and inositol phosphate, which serve as nutrients for bacterial growth and biofilm development. Additionally, PlcA modifies the bacterial cell surface, promoting adhesion and aggregation, which are essential for biofilm formation. The hbl operon encodes the tripartite hemolysin BL (Hbl) toxin, which promotes bacterial aggregation. Finally, InhA2, a zinc-dependent metalloprotease, modulates the bacterial cell surface, enhancing adhesion and aggregation. |